Format

Send to

Choose Destination
Nat Commun. 2015 Jan 12;6:5970. doi: 10.1038/ncomms6970.

A fatty acid-dependent hypothalamic-DVC neurocircuitry that regulates hepatic secretion of triglyceride-rich lipoproteins.

Author information

1
Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario, Canada M5G 1L7.
2
1] Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario, Canada M5G 1L7 [2] Departments of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
3
Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
4
1] Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario, Canada M5G 1L7 [2] Departments of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 [3] Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8 [4] Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada M5G 2C4.

Abstract

The brain emerges as a regulator of hepatic triglyceride-rich very-low-density lipoproteins (VLDL-TG). The neurocircuitry involved as well as the ability of fatty acids to trigger a neuronal network to regulate VLDL-TG remain unknown. Here we demonstrate that infusion of oleic acid into the mediobasal hypothalamus (MBH) activates a MBH PKC-δ→KATP-channel signalling axis to suppress VLDL-TG secretion in rats. Both NMDA receptor-mediated transmissions in the dorsal vagal complex (DVC) and hepatic innervation are required for lowering VLDL-TG, illustrating a MBH-DVC-hepatic vagal neurocircuitry that mediates MBH fatty acid sensing. High-fat diet (HFD)-feeding elevates plasma TG and VLDL-TG secretion and abolishes MBH oleic acid sensing to lower VLDL-TG. Importantly, HFD-induced dysregulation is restored with direct activation of either MBH PKC-δ or KATP-channels via the hepatic vagus. Thus, targeting a fatty acid sensing-dependent hypothalamic-DVC neurocircuitry may have therapeutic potential to lower hepatic VLDL-TG and restore lipid homeostasis in obesity and diabetes.

PMID:
25580573
DOI:
10.1038/ncomms6970
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center